A new national cohort study published in JAMA provides one of the most extensive looks to date at long-term mortality after COVID-19 mRNA vaccination. The findings, drawn from French national health data and covering nearly 28 million adults, show no increase in four-year all-cause mortality among vaccinated individuals aged 18 to 59. Researchers also reported substantially lower death rates among vaccinated adults, including from severe COVID-19.
The study addresses a gap in existing research. While earlier work evaluated short-term risks following vaccination, few analyses have compared multi-year mortality outcomes by vaccination status—particularly in younger and middle-aged adults who generally face lower risks of severe COVID-19.
A National Dataset Covering Millions
The research team examined records for 22.7 million vaccinated individuals and 5.9 million unvaccinated individuals who were alive in France on November 1, 2021. Vaccinated individuals were those who received their first mRNA dose between May and October 2021. Individuals who were unvaccinated by November 1, 2021, were assigned a random index date based on vaccinated individuals’ vaccination dates.
Key Findings
During the study period, 98,429 deaths occurred among vaccinated adults (0.4%) compared with 32,662 deaths among unvaccinated adults (0.6%). Across multiple analyses, vaccinated individuals showed consistently lower mortality:
-
74% lower risk of death from severe COVID-19 (weighted hazard ratio (wHR) 0.26).
-
25% lower risk of all-cause mortality (wHR 0.75).
-
Similar reductions even when excluding deaths attributed to severe COVID-19.
-
Lower mortality across categories in sensitivity analyses.
-
A separate short-term analysis found a 29% reduction in mortality within six months of vaccination.
While vaccinated individuals tended to be slightly older, more often women, and more likely to have cardiometabolic conditions, their mortality outcomes remained more favorable over time.
Context for Long-Term Safety
The study’s authors noted that while early analyses of vaccine safety focused on immediate adverse events—such as rare cases of myocarditis or anaphylaxis—long-term mortality patterns had not been well-characterized. Previous short-term evaluations found no increased risk of major cardiovascular events and suggested potential reductions in non-COVID mortality, though these findings required longer-term investigation.
With the COVID-19 pandemic resulting in more than 7 million deaths worldwide by early 2025, understanding the long-term safety profile of vaccines remains a central public health priority.
Conclusion
The study’s conclusion is clear: among adults aged 18 to 59, mRNA COVID-19 vaccination was not associated with any increase in four-year all-cause mortality. Instead, vaccinated individuals showed substantially lower mortality overall, including from severe COVID-19.
As mRNA vaccines continue to be widely used across the world, the authors note that these findings add another layer of evidence supporting their long-term safety.
Read the original article and findings in full here.
(AI was used in part to facilitate this article.)